The overall objective of this program is to develop implantable microreactors containing islets from animal sources for treatment of diabetic patients. These spherical microreactors are permselective to permit penetration of lower molecular weight substances including nutrients, electrolytes, oxygen and bioactive secretory products such as insulin, while excluding immunocytes, antibodies, complement and other transplant rejection effector molecule. These microreactors are of sufficiently small diameter that they can be injected subcutaneously, intraperitoneally or in other sites simply by using a hypodermic syringe and needle. This approach does not require a life long regimen of immunosuppressive drugs with serious side effects. In addition, it does not require costly and complicated surgery, and offers a solution to the presently insurmountable problem of procuring sufficient numbers of human pancreatic organs by permitting xenografting of islets from animal sources. Successful Phase I research focused on development of technology required to fabricate these microreactors, and on in vitro studies of islet viability and function. The proposed Phase II studies will build upon these findings. Microreactor designs and fabrication techniques will be further refined. The in vivo effects of implanted microreactors containing islets from animal sources on glucose homeostasis in diabetic rats and dogs will be examined in detail. A preferred microreactor design and fabrication protocol will be developed for testing in diabetic patients. PROPOSED COMMERCIAL APPLICATION: Development of implantable microreactors would enable transplantation of islets isolated from animals into diabetic patients without requiring a life long regimen of immunosuppressive drugs.